Many patients with kidney cancer who had been
exposed to high levels of trichloroethylene have a unique pattern of
genetic mutations within their cancerous cells. These findings were
reported by Hiltrud Brauch, PhD, of the University of Hamburg,
Germany (currently at the Dr. Margarete Fischer-Bosch-Institute of
Clinical Pharmacology, Stuttgart), and colleagues, in the May 19,
1999, issue of the Journal of the National Cancer Institute.
The authors studied 44 patients with renal cell carcinoma who had
been employed in metal processing factories. At the time of their
employment, trichloroethylene was widely used as a degreaser, and
minimal precautions were taken to prevent workers from exposure to
the solvent. An exposure level was determined for each patient by
calculating the duration, frequency, and mode of exposure and by
ascertaining the presence of any symptoms. Levels of exposure were
classified as high, medium, and low.
Mutations in Tumor-Suppressor Gene
The researchers looked for mutations of the von Hippel-Lindau (VHL)
tumor-suppressor gene in the DNA extracted from the normal and
cancerous tissues of these 44 patients. Control samples from 107
patients with renal cell carcinoma but without known exposure to
trichloroethylene were analyzed, and lymphocyte DNA from the 44 study
subjects and 97 healthy subjects was tested as well.
Mutations of the VHL gene were found in 33 (75%) of 44 tumors of the
workers who had been exposed to trichloroethylene. Among the patients
who exhibited mutations, 15 had experienced a high level of exposure
to the solvent and 18, a medium exposure level.
A particular mutational hot spot in the VHL gene was seen in the
tumors of many of the exposed workers. This mutation was not seen in
the lymphocyte DNA of the 44 workers, in lymphocytes from the 97
control subjects who did not have cancer, or in DNA from the tumors
of renal cell carcinoma patients who had not been exposed to trichloroethylene.
The authors note that their findings of unique and frequent VHL gene
mutations in the cancer cells of workers exposed to trichloroethylene
represent the first molecular evidence of a relationship between
exposure to a defined carcinogen, gene damage, and kidney cancer.